There is evidence that dietary factors, particularly fat intake are involved in the etiology of breast cancer. In addition, there are numerous studies showing that estrogen may also affect the incidence of breast cancer. The initial 2 1/4 years of this grant studies the influence of dietary fat and fiber on estrogen metabolism in premenopausal women. We found that merely reducing total dietary fat (40% to 25% of total calories) and increasing fiber, without changing dietary cholesterol or the P:S ratio had no effect on estrogen metabolism. However, when dietary cholesterol was reduced from 400 mg to 150 mg and the P:S ratio was changed from 0.5 to 1.0, then the low fat diet did indeed alter estrogens. Specifically, serum estrone sulfate was significantly reduced, and decreased oxidation of estradiol at the 16 position resulted in lower urinary excretion of 16 -hydroxyestrone and estriol conjugates. We plan to continue our studies on the role of dietary fat in estrogen metabolism, focusing on the type and amount of dietary fat and cholesterol. By feeding carefully designed diets in our metabolic unit, we can alter total dietary fat and cholesterol, as well as the type and degree of saturation of dietary fatty acids. Besides varying the P:S ratio, we also plan to study the effects of 18:2 and omega-3 fatty acids on estrogen metabolism. Among the hormones to be studied are serum estrone, estradiol and estrone sulfate; urinary sulfate and glucuronide conjugates of 2-methoxyestrone and estradiol, 2-hydroxyestrone and estradiol, 16-hydroxyestrone, estrone, estradiol and estriol; fecal estrone, estradiol and estriol. A radiolabeled will be done on each diet using 14C-estradiol given intravenously and 3H-estradiol given orally. Serum cholesterol and its fractions, and triglycerides will also be examined on each diet. The initial studies will be done in premenopausal women. When the "optimal" diet has been determined in terms of influencing estrogen metabolism in premenopausal women, this diet will be given to two groups of healthy postmenopausal women, those who are at normal risk for developing breast cancer and those who are at high risk. Thus, it will be possible to observe the effect of diet on their estrogen patterns. The overall goal of these studies is to design a diet that will reduce breast cancer risk, based on estrogen metabolism.